Signal peptides help newly synthesized proteins reach the cell membrane or be secreted. As part of a biological process key to immune response and surveillance in humans, and associated with diseases, for example, Alzheimer, remnant signal peptides and other transmembrane segments are proteolyzed by the intramembrane aspartyl protease (IAP) enzyme family. Here, we identified IAP orthologs throughout the tree of life. In addition to eukaryotes, IAPs are encoded in metabolically diverse archaea from a wide range of environments. We found three distinct clades of archaeal IAPs: (a) Euryarchaeota (eg, halophilic Halobacteriales, methanogenic Methanosarcinales and Methanomicrobiales, marine Poseidoniales, acidophilic Thermoplasmatales, hyperthermophilic Archaeoglobus spp.), (b) DPANN, and (c) Bathyarchaeota, Crenarchaeota, and Asgard. IAPs were also present in bacterial genomes from uncultivated members of Candidate Phylum Radiation, perhaps due to horizontal gene transfer from DPANN archaeal lineages. Sequence analysis of the catalytic motif YD…GXGD (where X is any amino acid) in IAPs from archaea and bacteria reveals WD in Lokiarchaeota and many residue types in the X position. Gene neighborhood analysis in halophilic archaea shows IAP genes near corrinoid transporters (btuCDF genes). In marine Euryarchaeota, a putative BtuF‐like domain is found in N‐terminus of the IAP gene, suggesting a role for these IAPs in metal ion cofactor or other nutrient scavenging. Interestingly, eukaryotic IAP family members appear to have evolved either from Euryarchaeota or from Asgard archaea. Taken together, our phylogenetic and bioinformatics analysis should prompt experiments to probe the biological roles of IAPs in prokaryotic secretomes.

中文翻译：

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膜内天冬氨酰蛋白酶同胞的古生根信号肽肽酶和早老素。

信号肽可帮助新合成的蛋白质到达细胞膜或被分泌。作为对人类免疫应答和监视至关重要的生物过程的一部分，并且与疾病相关，例如，阿尔茨海默氏症，残余信号肽和其他跨膜片段由膜内天冬氨酰蛋白酶（IAP）酶家族进行蛋白水解。在这里，我们确定了整个生命树中的IAP直系同源物。除真核生物外，IAP还被编码在来自广泛环境的代谢多样的古细菌中。我们发现古单边行动计划的三个不同分支：（一）广古菌门（例如，嗜盐Halobacteriales，甲烷Methanosarcinales和Methanomicrobiales，海洋Poseidoniales的，嗜酸的Thermoplasmatales，超嗜热Archaeoglobus属物种），（b）中DPANN，和（c）Bathyarchaeota，泉古菌，和仙宫。IAPs还存在于未培养的候选Phylum辐射成员的细菌基因组中，这可能是由于从DPANN古细菌谱系进行水平基因转移所致。对古细菌和细菌的IAP中的催化基序YD…GXGD（其中X是任何氨基酸）的序列分析显示，Lokiarchaeota中的WD和X位置上的许多残基类型。嗜盐古细菌中的基因邻域分析表明，IAP基因位于类Corrinoid转运蛋白附近（btuCDF基因）。在海洋Euryarchaeota，在IAP基因的N端发现了一个假定的BtuF样结构域，表明这些IAP在金属离子辅因子或其他营养清除中的作用。有趣的是，真核IAP家族成员似乎是从Euryarchaeota或Asgard古细菌进化而来的。综上所述，我们的系统发育和生物信息学分析应促使进行实验，以探索IAP在原核分泌物组中的生物学作用。